Bottom Line:
However, this difference gradually disappeared over 6 weeks.The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

Objective: Type 1 and 2 diabetes are characterized by elevated blood glucose levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum. However, previous studies reported a negative correlation between glucose concentrations and DPP4 levels. The purpose of this study was to elucidate the connection between glucose and DPP4 in adipocytes under physiological and diabetic conditions, because DPP4 is an adipokine.

Methods: Blood glucose and serum DPP4 levels were measured, and adipocytes were collected from mice under normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1 preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from mice and 3T3-L1 were stimulated by tumor necrosis factor-α (TNF-α) for 24 hours. The levels of released and intracellular DPP4 were determined by enzyme-linked immunosorbent assay.

Results: Mice fed high-fat diet had lower serum DPP4 levels in the first and second week than controls. However, this difference gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes under 25 mM glucose produced lower DPP4 levels than those differentiated under 5.5 mM; this was also observed in isolated adipocytes from mice. However, these effects of glucose were lost in adipocytes from diabetic mice, and an increase in total DPP4 levels was observed. The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.

Conclusion: The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose under physiological conditions, but not in diabetic mice. Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

Mentions:
We first examined the effects of the high-fat diet, which induced an increase in body weight (Figure 1A) and serum glucose levels (Figure 1B), on serum DPP4 levels. Mice fed the high-fat diet for 1 week had lower serum DPP4 levels than those in mice fed the normal chow diet; however, these differences in serum DPP4 levels gradually disappeared with continuous feeding of the high-fat diet (Figure 1C). A plot of blood glucose levels and serum DPP4 revealed a negative correlation at Weeks 1 and 2, which gradually became positive after 4 weeks of feeding with the high-fat diet (Figure 1D). To determine whether DPP4 levels varied under the fasting and fed conditions, we performed an oral glucose tolerance test in overnight-fasted mice. The oral administration of glucose (1.5 g/kg) had no effect on serum DPP4 levels (Figure 1E), although blood glucose levels increased as expected from the oral glucose tolerance test of normal chow-fed mice (Figure 1F). These results suggested that the decrease observed in serum DPP4 levels in high-fat diet-fed mice in 1 week was not a short-term process.

Mentions:
We first examined the effects of the high-fat diet, which induced an increase in body weight (Figure 1A) and serum glucose levels (Figure 1B), on serum DPP4 levels. Mice fed the high-fat diet for 1 week had lower serum DPP4 levels than those in mice fed the normal chow diet; however, these differences in serum DPP4 levels gradually disappeared with continuous feeding of the high-fat diet (Figure 1C). A plot of blood glucose levels and serum DPP4 revealed a negative correlation at Weeks 1 and 2, which gradually became positive after 4 weeks of feeding with the high-fat diet (Figure 1D). To determine whether DPP4 levels varied under the fasting and fed conditions, we performed an oral glucose tolerance test in overnight-fasted mice. The oral administration of glucose (1.5 g/kg) had no effect on serum DPP4 levels (Figure 1E), although blood glucose levels increased as expected from the oral glucose tolerance test of normal chow-fed mice (Figure 1F). These results suggested that the decrease observed in serum DPP4 levels in high-fat diet-fed mice in 1 week was not a short-term process.

Bottom Line:
However, this difference gradually disappeared over 6 weeks.The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

Objective: Type 1 and 2 diabetes are characterized by elevated blood glucose levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum. However, previous studies reported a negative correlation between glucose concentrations and DPP4 levels. The purpose of this study was to elucidate the connection between glucose and DPP4 in adipocytes under physiological and diabetic conditions, because DPP4 is an adipokine.

Methods: Blood glucose and serum DPP4 levels were measured, and adipocytes were collected from mice under normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1 preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from mice and 3T3-L1 were stimulated by tumor necrosis factor-α (TNF-α) for 24 hours. The levels of released and intracellular DPP4 were determined by enzyme-linked immunosorbent assay.

Results: Mice fed high-fat diet had lower serum DPP4 levels in the first and second week than controls. However, this difference gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes under 25 mM glucose produced lower DPP4 levels than those differentiated under 5.5 mM; this was also observed in isolated adipocytes from mice. However, these effects of glucose were lost in adipocytes from diabetic mice, and an increase in total DPP4 levels was observed. The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.

Conclusion: The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose under physiological conditions, but not in diabetic mice. Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.